U.S. Pat. No. 5,116,863 discloses olopatadine (Z-11-[3-(dimethylamino)propylidene]-6,11-dihydrodibenz [b,e]oxepin-2-acetic acid) as a compound having an anti-allergic activity.
For ophthalmic use, U.S. Pat. No. 5,641,805 discloses topical ophthalmic formulations for treating allergic eye disease which comprise olopatadine as an active ingredient. This patent describes that a preferred formulation for topical ophthalmic administration is a solution, and the solution is administered in the form of eye drops.
Conventionally, the most common dosage form of topical ophthalmic formulations is eye drops. In fact, olopatadine hydrochloride is used in the form of eye drops for treating allergic conjunctivitis. However, eye drops show low local bioavailability due to the turnover of tear fluid on the surface of the eye, and thus eye drops must be frequently administered in order to maintain a pharmacological effect on the eye. For example, commercially available eye drops comprising olopatadine hydrochloride must be administered every 6 to 8 hours (i.e. twice or more a day). In addition, many eye drops contain a preservative. As a result of the use of such eye drops over a prolonged period, the preservative could cause adverse side effects such as irritation.
In view of the above, the development of an ophthalmic preparation for treating allergic eye disease such as allergic conjunctivitis, which can persistently deliver a therapeutically effective amount of a drug to an anterior ocular segment such as conjunctiva, exert a pharmacological effect on the segment over a prolonged period, and which can decrease the risk of adverse side effects, as compared to conventional preparations such as eye drops has been desired.
One of such ophthalmic preparations is reported in WO2004/064817. WO2004/064817 discloses a percutaneously absorptive preparation which is composed of a support and a plaster layer containing a therapeutic agent for eye disease formed on the support, and applied to the skin surface including the anterior surface of an eyelid in order to transfer the therapeutic agent contained in the plaster layer to the local tissues of the eye through the skin instead of a systemic blood flow. This preparation can transfer the therapeutic agent to external eye tissues such as conjunctiva, lacrimal tissue and cornea through the skin in relatively a short time, and exert a prolonged pharmacological effect on the tissues. As a therapeutic agent for eye disease, WO2004/064817 discloses ketotifen fumarate.
However, WO2004/064817 does not disclose use of olopatadine for percutaneously absorptive preparations. In addition, U.S. Pat. No. 5,641,805 does not disclose percutaneously absorptive preparation as a dosage form of olopatadine.